PROJECT SUMMARY This R01 renewal application proposes functional neuroimaging studies with human subjects to elucidate the role of the prefrontal cortex and amygdala in the processing of facial identities and expressions that predict critical social outcomes. Presentations of facial expressions of emotion in neuroimaging studies have proven particularly robust stimuli for activating amygdala and prefrontal regions involved in processing biologically- relevant social cues. Here we propose to further develop our novel structural and functional neuroimaging methods to better understand how the amygdala interacts with reciprocally connected prefrontal areas when such expressions are encountered. Specifically, following up on our previous findings that the structural integrity of an amygdala-prefrontal pathway predicts individual differences in reported anxiety ? we replicated this effect in > 250 subjects and observed an exciting sex difference; this effect is compellingly stronger in females than in males. Here we propose to follow up on this effect with higher resolution DTI methods and to extend it to functional resting state data to see if the same sex difference is observed functionally. In addition, we propose a new mathematical model where we believe we can disentangle the effects of valence from arousal in brain imaging data, a confound the field continues to struggle with. Finally, we propose the development of a new facial expression stimulus set where we record the psychological status of the models posing for the expressions so we can determine any interaction this might have with the psychological status of the our subjects of study. The field can then usefully compare these data to complementary developmental research (i.e., with children and adolescents) and will be amenable to direct translation to clinical populations (e.g., anxiety and depression).